P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer

Ono, Hiroaki; Basson, Marc D.; Ito, Hiromichi

doi:10.18632/oncotarget.10117

Cited by 51 publications

(41 citation statements)

References 29 publications

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“…We have previously shown that the two HAT inhibitors, ICG-001 and C646, differentially impair the global gene expression levels in human pancreatic and colorectal cancer cell lines [37]. Additionally, other work has shown that ICG-001 and C646 reduce tumorigenicity of pancreatic cancer cell models [38][39][40] and ICG-001 has been used in clinical trials for pancreatic cancer (NCT01302405). However, the impact of HAT inhibitor treatment on histone acetylation remains unknown.…”

Section: Histone Acetyltransferase Inhibitors Alter Global H3k27ac Anmentioning

confidence: 99%

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

et al. 2019

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The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, we characterized the broad domains from different pancreatic ductal adenocarcinoma (PDAC) cell lines that represent distinct histological grades. Our integrative genomic analysis found that human derived cell line models for distinct PDAC grades exhibit characteristic broad epigenetic features associated with gene expression patterns that are predictive of patient prognosis and provide insight into pancreatic cancer cell identity. In particular, we find that genes marked by overlapping Low-Grade broad domains correspond to an epithelial phenotype and hold potential as markers for patient stratification. We further utilize ChIP-seq to compare the effects of histone acetyltransferase (HAT) inhibitors to detect global changes in histone acetylation and methylation levels. We found that HAT inhibitors impact certain broad domains of pancreatic cancer cells. Overall, our results reveal potential roles for broad domains in cells from distinct PDAC grades and demonstrate the plasticity of particular broad epigenomic domains to epigenetic inhibitors.

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Section: Histone Acetyltransferase Inhibitors Alter Global H3k27ac Anmentioning

confidence: 99%

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

et al. 2019

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“…Furthermore, the expression of leptin in gastro-esophageal adenocarcinomas was associated with chemoresistance. The use of leptin receptor antagonist SHLA increased the sensitivity to Cisplatin in the resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33[134]. …”

Section: Pancreatic Cancer Stem Cellsmentioning

confidence: 99%

Leptin signaling and cancer chemoresistance: Perspectives

Candelaria¹,

Rampoldi²,

Harbuzariu³

et al. 2017

WJCO

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Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro-tumorigenic adipokine that has been implicated in many cancers promoting processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance to apoptosis. Several possible mechanisms that could potentially be developed by cancer cells to elicit drug resistance have been suggested in the literature. Here, we summarize and discuss the current state of the literature on the role of obesity and leptin on chemoresistance, particularly as it relates to breast and pancreatic cancers. We focus on the role of leptin and its significance in possibly driving these proposed chemoresistance mechanisms, and examine its effects on cancer cell survival signals and expansion of the cancer stem cell sub-populations.

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“…However, P300 overexpression was not significantly associated with OS. Although P300 has been observed as a tumour suppressor in the majority of studies, its oncogenic role has also been confirmed in multiple cancer types, where it is involved in the EMT (23,27,28), proliferation (29,30) and apoptosis (30,31). Gao et al (16) suggested that high expression of P300 enhanced EMT of HCC cells, and Liao et al (27) also indicates that P300 promotes EMT in an NPC cell line.…”

Section: Discussionmentioning

confidence: 99%

“…Inagaki et al (29), indicated that core-binding protein/P300 histone acetyltransferase activity is responsible for epigenetic regulation of proliferation and invasion in HCC cells, and Dou et al (32) suggested that midazolam inhibits the proliferation of human head and neck SCC cells by downregulating P300 expression. Gao et al (30) reported that the P300 inhibitor C646 induces cell cycle arrest and apoptosis in acute myeloid leukemia cells and Ono et al (31) indicated that P300 inhibition enhances the gemcitabine-induced apoptosis of pancreatic cancer cells. Table IV.…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of upregulated P300 expression in human cancers: A clinical study of synovial sarcoma and a meta‑analysis

Liu

Lian

et al. 2019

Exp Ther Med

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E1A binding protein p300 (P300) is a member of the histone acetyltransferase family of transcriptional co-activators, which are associated with various types of cancer. Numerous studies have evaluated the diagnostic value of P300, but their results are not consistent. Therefore, a clinical study and a meta-analysis were performed in the present study to investigate the prognostic value of P300 expression in human malignant neoplasms. Immunohistochemical (IHC) analysis was used to assess P300 expression in 43 paraffin-embedded primary synovial sarcoma (SS) samples. For the meta-analysis, eligible studies published until January 21, 2018 were identified by searching the PubMed, EMBASE and Web of Science databases. The IHC analysis indicated a high P300 expression rate in 33.3% (10/30) of biphasic SS (BSSs) and in 60% (6/10) of monophasic fibrous SS tissues. In BSS, the expression rate was significantly higher in the epithelial component (80.0%, 24/30) than that in the spindle-cell component (30.0%, 9/30; P<0.05). The meta-analysis indicated that high expression of P300 was associated with poor overall survival (OS) in digestive system malignant neoplasms (HR=1.54, 95% CI: 1.20-2.23), as well as with poor progression-free survival, recurrence-free survival and disease-free survival combined (HR=1.84, 95% CI: 1.36-2.47). Analysis of subgroups by ethnicity demonstrated that high expression of P300 was associated with poor OS in Asians (HR=1.72, 95% CI: 1.20-2.47) but favourable OS in Caucasians (HR=0.59, 95% CI: 0.47-0.73). Furthermore, high expression of P300 was associated with clinical stage [Relative Risk (RR)=1.30, 95% CI: 1.07-1.58], lymph node metastasis (RR=1.30, 95% CI: 1.03-1.64) and depth of invasion (RR=1.31, 95% CI: 1.07-1.60). P300 expression may therefore be a useful biomarker for predicting patient prognosis in various types of human cancer.

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P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer

Cited by 51 publications

References 29 publications

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

Leptin signaling and cancer chemoresistance: Perspectives

Prognostic role of upregulated P300 expression in human cancers: A clinical study of synovial sarcoma and a meta‑analysis

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